2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)

Matthew G. Bursavich; Daniel P. Parker; J. Adam Willardsen; Zhong Hua Gao; Thaylon Davis; Kirill Ostanin; Rosann Robinson; Ashley Peterson; Daniel M. Cimbora; Ju Fen Zhu; Burt Richards

doi:10.1016/j.bmcl.2010.01.058

2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)

Matthew G. Bursavich
, Daniel P. Parker
, J. Adam Willardsen
, Zhong Hua Gao
, Thaylon Davis
, Kirill Ostanin
, Rosann Robinson
, Ashley Peterson
, Daniel M. Cimbora
, Ju Fen Zhu
, Burt Richards

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase family with a central role in the ubiquitin-degradation of misfolded proteins. VCP also exhibits antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1,3-thiazoles are potent drug-like inhibitors of this enzyme. The identified compounds show low nanomolar VCP potency, demonstrate SAR trends, and show activity in a mechanism based cellular assay. This series of compounds represents the first steps towards a novel, small molecule VCP inhibitor as a cancer therapeutic.

Original language	English (US)
Pages (from-to)	1677-1679
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2010.01.058
State	Published - Mar 1 2010

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2010.01.058

Cite this

@article{cfad9fa5f28a4a0eb57e0178477e0f2a,

title = "2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)",

abstract = "Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase family with a central role in the ubiquitin-degradation of misfolded proteins. VCP also exhibits antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1,3-thiazoles are potent drug-like inhibitors of this enzyme. The identified compounds show low nanomolar VCP potency, demonstrate SAR trends, and show activity in a mechanism based cellular assay. This series of compounds represents the first steps towards a novel, small molecule VCP inhibitor as a cancer therapeutic.",

author = "Bursavich, \{Matthew G.\} and Parker, \{Daniel P.\} and Willardsen, \{J. Adam\} and Gao, \{Zhong Hua\} and Thaylon Davis and Kirill Ostanin and Rosann Robinson and Ashley Peterson and Cimbora, \{Daniel M.\} and Zhu, \{Ju Fen\} and Burt Richards",

year = "2010",

month = mar,

day = "1",

doi = "10.1016/j.bmcl.2010.01.058",

language = "English (US)",

volume = "20",

pages = "1677--1679",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "5",

}

TY - JOUR

T1 - 2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)

AU - Bursavich, Matthew G.

AU - Parker, Daniel P.

AU - Willardsen, J. Adam

AU - Gao, Zhong Hua

AU - Davis, Thaylon

AU - Ostanin, Kirill

AU - Robinson, Rosann

AU - Peterson, Ashley

AU - Cimbora, Daniel M.

AU - Zhu, Ju Fen

AU - Richards, Burt

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase family with a central role in the ubiquitin-degradation of misfolded proteins. VCP also exhibits antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1,3-thiazoles are potent drug-like inhibitors of this enzyme. The identified compounds show low nanomolar VCP potency, demonstrate SAR trends, and show activity in a mechanism based cellular assay. This series of compounds represents the first steps towards a novel, small molecule VCP inhibitor as a cancer therapeutic.

AB - Valosin-containing protein (VCP; also known as p97) is a member of the AAA ATPase family with a central role in the ubiquitin-degradation of misfolded proteins. VCP also exhibits antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. We have discovered that 2-anilino-4-aryl-1,3-thiazoles are potent drug-like inhibitors of this enzyme. The identified compounds show low nanomolar VCP potency, demonstrate SAR trends, and show activity in a mechanism based cellular assay. This series of compounds represents the first steps towards a novel, small molecule VCP inhibitor as a cancer therapeutic.

UR - https://www.scopus.com/pages/publications/76649137232

UR - https://www.scopus.com/pages/publications/76649137232#tab=citedBy

U2 - 10.1016/j.bmcl.2010.01.058

DO - 10.1016/j.bmcl.2010.01.058

M3 - Article

C2 - 20137940

AN - SCOPUS:76649137232

SN - 0960-894X

VL - 20

SP - 1677

EP - 1679

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

2-Anilino-4-aryl-1,3-thiazole inhibitors of valosin-containing protein (VCP or p97)

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this